Phospholipase A2 (PLA2) is a protein (16,000 atoms) which complexes with membrane surfaces, destabilizes a phospholipid, extracts it from the membrane, and catalyzes the hydrolysis reaction of the sn-2-acyl chain of the lipid [14-16]. One of the reaction products, arachidonic acid, is an important metabolic intermediate producing eicosanoids, which are regulatory factors implicated in a wide range of physiological and pathological states [101]. The interfacial catalysis of PLA2 involves four reaction steps: complex formation, scooting on the surface, lipid extraction from the membrane, and the hydrolysis reaction. We had previously modeled the formation of the complex of human synovial phospholipase A2 with a membrane [102]. Steered molecular dynamics simulations [3, 4, 6, 8, 100] were employed to investigate the lipid extraction step by pulling a lipid molecule from a monolayer of dilauroyl-phosphatidyl-ethanolamin (DLPE) lipids into the active site of PLA2 and into th e aqueous phase* [5]. External forces were applied to the head group of the lipid, pulling it out from the membrane. The forces required to displace the lipid from the membrane into the binding pocket of PLA2 were larger than those required to displace the lipid from the membrane into the aqueous phase. The simulations showed that in the presence of PLA2 the hydrogen bonds are formed between the phosphate and amino groups of the extracted lipid and the corresponding groups of the neighboring lipids. These bonds had to be broken in order to extract the lipid from the monolayer. In the absence of PLA2, however, the lipid head groups were well solvated and did not form hydrogen bonds with each other. These results do not agree with the hypothesis of destabilization of the lipids by PLA2, facilitating lipid extraction by the enzyme. The disagreement may have resulted from the steric effects mentioned above, an imperfect choice of the pulling direction for the lipid extraction into the enzyme, or insufficient sampling due to the short (500 ps) simulation time.